Artifact Control and Miniaturization of the Safe Direct Current Stimulator for Neural Prostheses

ABSTRACT

An embodiment in accordance with the present invention provides a device and method to deliver direct ionic current safely to target neural tissue, while also eliminating interruptions in the output of the device that can result from the non-ideal operation of the valves used to control the current flow in the device. The device includes two valve-operated systems that work in tandem. The first and second current producing systems are configured to be used together in order to eliminate the periodic interruptions in current flow. In use, one system drives current through the target tissue, while the other system closes all of the valves first and then opens its valves in sequence. This intermediate step of closing all of the valves prevents unintended current shunts through either system. The device also includes two conductors to direct the flow of direct current into the target tissue.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 61/577,821, filed Dec. 20, 2011, which is incorporatedby reference herein, in its entirety.

GOVERNMENT SUPPORT

This invention was made with government support under NIH R01DC009255awarded by the National Institute of Health. The government has certainrights in the invention.

FIELD OF THE INVENTION

The present invention relates generally to neural stimulation. Moreparticularly, the present invention relates to a device and method fordelivering DC current to target tissue.

BACKGROUND OF THE INVENTION

While effective in treating some neurological disorders, neuralprostheses are limited because they can excite neurons but notefficiently inhibit them. Direct current (DC) applied to a metalelectrode in contact with neural tissue can excite or inhibit neuralactivity; however, DC stimulation is biologically unsafe because itcauses electrochemical reactions at the metal electrode-tissueinterface. To avoid these safety hazards, neural prostheses generallydeliver alternating current (AC) pulses to evoke action potentials.

While cochlear and retinal prostheses use AC pulses to encode sensoryinformation by modulating firing rate of the afferent fibers above theirspontaneous activity, other neural prosthesis applications havesubstantial difficulties achieving effective treatment with excitationalone. A prosthesis to assist micturition, for instance, requires bothexcitation of sacral nerves to activate the detrusor muscle andsimultaneous inhibition of lumbar nerves to relax the urethralsphincter. For proper balance as well, inner ear vestibular afferentfibers require not only excitation to encode head motion toward thestimulated side of the head, but also inhibition to encode head motionaway from it. In restoring normal physiology, therefore, the ability fora neural prosthesis to both inhibit and excite neurons would be useful.Furthermore, several disorders characterized by high neural firing ratessuch as tinnitus, chronic pain, and epilepsy could be effectivelytreated by prostheses capable of neural inhibition. Gradual modulationof extracellular potential rather than evoking or inhibiting spikescould further extend the capabilities of neural prostheses to treatingdisorders such as autism by addressing excitatory vs inhibitoryimbalance, and DC potential support to treat strial hearing loss.

At low amplitudes, DC can achieve graded control of neural activity byaltering the extracellular electric field near the electrode. Byaltering the electric field, DC modulates neural firing thresholds,increasing or decreasing the likelihood of spike initiation. At higherDC amplitudes, cathodic current excites neurons, while anodic currentinhibits them. DC stimulation that does not produce electrochemicalreactions at the electrode-saline interface could enable more versatiletreatments of neurological disorders than what is currently possible.

A solution to the problem of DC stimulation safety is to direct the DCflow of ions into the target tissue by switching mechanical valves inphase with AC square waves applied to the electrodes, which are immersedin an ionic solution. This approach removes DC from the electrode-salineinterface, while maintaining DC ionic current through the tissue. FIG.1A shows the two potential states of the system. FIG. 1B shows theoutput of the fully-functioning SDCS as the valves operate in synchronywith AC delivered to the electrodes. One important aspect of this deviceis that it works in a bipolar configuration so that the ions flowinginto one tube are replenished by the same types of ions flowing out ofthe other tube thus resulting in net zero ionic change in the tissuebetween the two tubes. This configuration addresses pH changes thatcould potentially be harmful to the neural tissue.

The fidelity of the DC signal is degraded by periodic interruptions incurrent flow due to non-ideal behavior of the mechanical valves used inthe device, as illustrated in FIG. 1B. The interruptions occur becauseionic current bypasses the tissue when the valves are temporarily andsimultaneously either open or closed during open-to-close andclose-to-open transitions. For example, if B2 and A2 are both closedduring a transition, no current will flow through the tissue. Theduration of the interruptions depends on the speed of the valvetransitions from open-to-close and from close-to-open states. Anyinterruption in the DC current flow however will cause the undesirablevolley of neural activity in the target neurons.

It would therefore be advantageous to provide a method to remove theinterruptions in the ionic direct current flow.

SUMMARY OF THE INVENTION

The foregoing needs are met, to a great extent, by the presentinvention, wherein in one aspect, a device for delivering direct currentincludes a first set of two electrodes and a second set of twoelectrodes configured to receive alternating current. The device alsoincludes a first set of valves. The first set of valves includes a firstand second pair of valves. The device also includes a second set ofvalves. The second set of valves includes a third and fourth pair ofvalves. The first and second sets of valves are configured to be openedand closed and are further configured to switch in phase with thealternating current applied to the first electrode and the secondelectrode. A tube is filled with conductive material and configured todirect the direct current flow of ions into target tissue. Additionally,the device is configured such that the first set of valves is closedwhen the third and fourth pairs of valves are being opened and thesecond set of valves is closed when the first and second pairs of valvesare being opened.

In accordance with another aspect of the present invention, two systemswork in tandem. In the arrangement described in the present invention,one system controls the ionic current system output to the tissue, whilethe second system undergoes valve transitions without affecting thedevice output. After the valves transition states in the second system,control of the device output switches electronically from the firstsystem to the second thus allowing the first system to switch its valveswithout affecting the device output. In this way, the smooth ioniccurrent output of the device is maintained independent of the valvetransition speed.

In accordance with an aspect of the present invention, the conductortakes the form of a tube defining a hollow lumen extending therethrough.The hollow lumen of the tube is filled with a conductive material, andthe conductive material is an ionic solution or an ionic hydrogel. Thesystem further includes a housing having multiple layers. Each one ofthe layers of the housing contains one of the electrodes or the firstset of valves and the second set of valves. Layer 1 of the housingcontains channels filled with an ionic solution or electrolytic gel toconduct ionic current flow. Layer 2 encloses and protects layer 1 andprovides openings through which the channels in layer 1 can be connectedor disconnected to control the ionic current flow through them. Layers 3and 4 add the ability to mechanically connect or disconnect the channelsvia the openings in Layer 2, forming the valves used to operate thedevice. The valves can take the form of mechanical valves, bridgerectifiers, or ionic diodes. Additionally, the mechanical valves can beactuated using Nitinol wire.

In accordance with another aspect of the present invention, a method fordelivering direct current includes applying alternating current toelectrodes immersed in an ionic solution. The method also includesclosing a first set of valves and switching a second set of valves insequence and in phase with the alternating current. Additionally themethod includes directing the direct current flow of ions into a targettissue.

In accordance with yet another aspect of the present invention, thefirst set of valves includes a first and second pair of valves and thesecond set of valves comprises a third and fourth pair of valves. Thefirst and second set of valves are configured to be opened and closedand are further configured to switch in phase with alternating currentapplied to the electrodes. A conductor is used to direct the directcurrent flow of ions into the target tissue. The conductor includes atube defining an elongate inner lumen, and the elongate inner lumen ofthe tube is filled with a conductive material. The conductive materialis an ionic solution or an ionic hydrogel. The method further includesclosing the first set of valves when the third and fourth pair of valvesare open, and closing the second set of valves when the first and secondpairs of valves are open.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings provide visual representations which will beused to more fully describe the representative embodiments disclosedherein and can be used by those skilled in the art to better understandthem and their inherent advantages. In these drawings, like referencenumerals identify corresponding elements and:

FIG. 1A illustrates a schematic diagram of the fundamental conceptbehind providing direct current stimulation to the tissue, whiledelivering alternating current to the metal electrodes within thedevice. Two states of the same system are shown.

FIG. 1B demonstrates the periodic interruptions that occur at the systemoutput from the prototype of the device described in FIG. 1A. Theinterruptions occur at every phase transition of the alternating currentand valve states.

FIG. 2 illustrates a device for delivering direct current flow to targettissue and configured to eliminate current interruptions, according toan embodiment of the present invention.

FIG. 3A illustrates the layer components for construction of the systemdescribed in FIG. 2 according to an embodiment of the present invention.

FIG. 3B illustrates the components of the system illustrated in FIG. 3Aassembled into the finished device.

FIG. 3C illustrates the location of the four metal electrodes relativeto the other components of the device.

FIG. 4 illustrates a block diagram of electronics for the device,according to an embodiment of the present invention.

FIG. 5 illustrates one of the two tube conductors (Tube electrode (TE))used to deliver the ionic current from the device to the neural tissue,according to an embodiment of the present invention.

DETAILED DESCRIPTION

The presently disclosed subject matter now will be described more fullyhereinafter with reference to the accompanying Drawings, in which some,but not all embodiments of the inventions are shown. Like numbers referto like elements throughout. The presently disclosed subject matter maybe embodied in many different forms and should not be construed aslimited to the embodiments set forth herein; rather, these embodimentsare provided so that this disclosure will satisfy applicable legalrequirements. Indeed, many modifications and other embodiments of thepresently disclosed subject matter set forth herein will come to mind toone skilled in the art to which the presently disclosed subject matterpertains having the benefit of the teachings presented in the foregoingdescriptions and the associated Drawings. Therefore, it is to beunderstood that the presently disclosed subject matter is not to belimited to the specific embodiments disclosed and that modifications andother embodiments are intended to be included within the scope of theappended claims.

An embodiment in accordance with the present invention provides a deviceand method to deliver direct current to a target tissue, while alsoeliminating interruptions in current flow. Two systems are used intandem to deliver uninterrupted current to the neural tissue via twoconductors. The two conductors (a.k.a. Tube electrode) are used todirect the flow of ionic current from the device into the target tissue.The first and second current producing systems are configured to be usedtogether in order to eliminate the periodic interruptions in currentflow. In use, one system drives current through the target tissue, whilethe other system closes all of the valves first and then opens itsvalves in sequence. This intermediate step of closing all of the valvesprevents unintended current shunts through either system.

FIG. 2 illustrates a device for delivering direct current flow to targettissue and is configured to eliminate current interruptions, accordingto an embodiment of the present invention. As illustrated in FIG. 2, thedevice 10 includes a left system 12 and a right system 14, bothconfigured to deliver current to target tissue 16. The left system 12includes a pair of electrodes 18, 20 and the right system 14 includes apair of electrodes 22, 24. The electrodes 18, 20, and 22, 24 areconfigured to receive alternating current from current sources I1 or I2respectively. After the electrical current enters either the left systemor the right system it travels through a conductive material, such assaline, or any other suitable conductive material or solution known toone of skill in the art. The left system 12 includes valves A1, A2, B1,and B2, and the right system 14 includes valves C1, C2, D1, and D2. Thevalves can take the form of mechanical valves, other valve technologyknown to or conceivable by one of skill in the art. Additionally, thevalves can be miniaturized using micro-electrical-mechanicalminiaturization (MEMS) or other miniaturization technology. Valve A1 isalways in the same state as valve A2, valve B1 is always in the samestate as valve B2 and so on.

Additionally, FIG. 2 illustrates an example of flow of current 26between electrodes 18 and 20 through the device 10 in order to deliverthe current to the target tissue 16. In the example presented in FIG. 2,the electric ionic current 26 flows easily through any open valve, suchas, for example in FIG. 2, valves B1, B2, D1, and D2 and not through theclosed valves, such as indicated by valves A1, A2 and C1 and C2. Asnoted above, the device 10 uses a left system 12 and a right system 14.One system drives current through the tissue, while the other closes allvalves first and then opens the next set of valves in sequence. Table 1,below, shows the states of the device 10 for different valve closures.The states are entered sequentially and repeat after S12. The state ofthe device is indicated in the left column. The asterisks (*) indicate aswitch in the current source that is controlling the flow through thetissue from the previous state. “0” indicates that the valve is closed.“1” indicates that the valve is open. Current sources I1, I2 can eithercontrol flow from upper electrode to the lower electrode in each of thetwo systems, indicated by “+”; lower to upper electrode indicated by“−”; or be off, indicated by “0.” It should also be noted that thedirect current is delivered to the target tissue 16 from the top tubefilled with conductive fluid to the bottom tube.

TABLE 1 l1 A1 A2 B1 B2 C1 C2 D1 D2 l2 S1 − 0 0 1 1 0 0 1 1 0 *S2 0 0 0 11 0 0 1 1 + S3 0 0 0 0 0 0 0 1 1 + S4 0 1 1 0 0 0 0 1 1 + *S5 + 1 1 0 00 0 1 1 0 S6 + 1 1 0 0 0 0 0 0 0 S7 + 1 1 0 0 1 1 0 0 0 *S8 0 1 1 0 0 11 0 0 − S9 0 0 0 0 0 1 1 0 0 − S10 0 0 0 1 1 1 1 0 0 − *S11 − 0 0 1 1 11 0 0 0 S12 − 0 0 1 1 0 0 0 0 0

Although the device indicated by the FIG. 2 schematic can be built usingdifferent methodologies, FIG. 3A illustrates one embodiment of thedevice and components for the construction of the present invention.FIG. 3B illustrates the components of the device illustrated in FIG. 3Aassembled into the finished device, and FIG. 3C illustrates the locationof the electrodes relative to the other components of the device. Asillustrated in FIGS. 3A and 3C, layer 1, 28, includes electrodes 18, 20,22, and 24, and channels through which the current can flow through asaline solution. The channels correspond to those shown in FIG. 2. Layer1 channels are filled with saline or an ionic hydrogel (such as based onAgar or gelatin) to conduct ionic current. Layer 2, 30, protects andcovers layer 1, 28, and provides valve openings for the valves A1, A2,B1, B2, C1, C2, D1, and D2 to connect/disconnect the ionic current inthe layer 1 channels. A thin layer of silicone, not shown, is used tocover layer 2, 30, to insulate the saline/gel in the valves from valveplungers 32, disposed in layer 3, 34. Layer 3, 34, and layer 4, 36include the valve plungers and Nitinol wires 38 used to actuate thevalves. Each of the Nitinol wires 38 actuates one pair of valves. All ofthe layers are formed from plastic or any other suitable material andglued together with water resistant glue, sealer, or other suitableadhesive.

Further, as illustrated in FIG. 3B, the valves are driven by the Nitinolwires 38. When electrically activated, using a microcontrollercontrolled electronic circuit, described further herein, the Nitinolwires decrease in length by 5%, allowing the intended valve to open.Each Nitinol wire 38 drives a pair of valve actuators, A, B, C, and D.The valve opens when the normally-closed actuator is deformed by tensionapplied to it through the 100 μm diameter Nitinol wire. The wire isshortened in length, when heated to 70-90° C. by driving 180 mA throughthe wire. The plunger 32 returns to its original position and lengthensthe wire back to the original length when the current is off The wirecan undergo extraction-contraction cycles at up to 2 Hz.

FIG. 4 illustrates a block diagram of electronics for the device,according to an embodiment of the present invention. A power blockgenerates three power outputs. The first power output is 60V, 2 mA todrive the current sources I1 and I2. The second is 3V, 30 mA to supportthe electronics. The third is 1.5V, 800 mA used to drive the Nitinolactuators. The valve drivers A, B, C, D maintain the current through thecorresponding Nitinol actuators. I1/I2 Current driver can direct currentin either positive or negative direction through the corresponding pairsof electrodes. The differential amplifier detects the ion flow directedthrough the tissue and sends the proportional voltage signal to theI1/I2 current driver to control the output of the current source. Themicrocontroller (μC) controls the state machine of the device asindicated by Table 1.

Two tube electrodes (conductors) are used, as illustrated in FIG. 5 tocarry the direct ionic current from the device to the stimulated tissue.This figure shows the one such embodiment of the tube electrodescompared to a typical PtIr wire electrode used in neural stimulation.These tube conductors can be prepared by filling (TE) Eppendorf 20 μLcapillary tubes (0.25 mm OD, 0.2 mm ID) with a sterile mixture of agarand ionic solution. While the gel freely conducts the ionic current, itresists fluid motion in and out of the tube and it offers a physicalbarrier to biological contamination of the implanted tissue.

Far reaching plans to advance safe DC stimulation include use of ionicdiodes or ionic transistors that could modulate ionic conductance tocontrol ionic current flow instead of mechanical valves. The ionic diodetechnology is quickly evolving to create semi-permeable membranes thatare constructed to allow flow of ions in one direction but block theflow in the opposite direction. Because mechanical valves are thehighest power consuming elements in the SDCS, using ionic diodes thatconsume no power at all will significantly reduce power of the overallsafe DC system. Ionic diodes can be used instead of the valves in thesafe DC system construction in a way that is analogous to the use ofdiodes in a bridge rectifier configuration. A bridge rectifier is a4-diode electronic component commonly used in power supplies to switchAC to DC power. The ionic diodes will control ion flow instead ofelectron current flow controlled by conventional diodes.

Assuming the ionic diodes can be reduced in size, more extrememiniaturization of the described technology will also enable multiplestimulation channels to be delivered simultaneously to differentstimulation targets because several separate safe DC stimulators couldbe assembled on one device.

The many features and advantages of the invention are apparent from thedetailed specification, and thus, it is intended by the appended claimsto cover all such features and advantages of the invention which fallwithin the true spirit and scope of the invention. Further, sincenumerous modifications and variations will readily occur to thoseskilled in the art, it is not desired to limit the invention to theexact construction and operation illustrated and described, andaccordingly, all suitable modifications and equivalents may be resortedto, falling within the scope of the invention.

Although the present invention has been described in connection withpreferred embodiments thereof, it will be appreciated by those skilledin the art that additions, deletions, modifications, and substitutionsnot specifically described may be made without departing from the spiritand scope of the invention as defined in the appended claims.

1. A device for delivering direct current, comprising: a first set oftwo electrodes and a second set of two electrodes configured to receivealternating current; a first set of valves, wherein the first set ofvalves comprises a first and second pair of valves, and a second set ofvalves, wherein the second set of valves comprises a third and fourthpair of valves, where the first and second sets of valves are configuredto be opened and closed and are further configured to switch in phasewith the alternating current applied to the first electrode and thesecond electrode; a tube filled with conductive material and configuredto direct the direct current flow of ions into target tissue; andwherein the device is configured such that the first set of valves isclosed when the third and fourth pairs of valves are being opened andthe second set of valves is closed when the first and second pairs ofvalves are being opened.
 2. The device of claim 1 wherein the conductorcomprises a tube defining a hollow lumen extending therethrough.
 3. Thedevice of claim 2 wherein the hollow lumen of the tube is filled with aconductive material.
 4. The device of claim 3 wherein the conductivematerial is an ionic solution or an ionic hydrogel.
 5. The device ofclaim 1 further comprising a housing.
 6. The device of claim 5 whereinthe housing comprises layers.
 7. The device of claim 6 wherein each oneof the layers of the housing contains one of the electrodes and thefirst set of valves and the second set of valves.
 8. The device of claim1 wherein the valves comprise mechanical valves.
 9. The device of claim8 wherein the mechanical valves comprise Nitinol wire.
 10. The device ofclaim 1 wherein the valves comprise a bridge rectifier.
 11. The deviceof claim 1 wherein the valves comprise an ionic diode.
 12. A method fordelivering direct current comprising: applying alternating current toelectrodes immersed in an ionic solution; closing a first set of valves;switching a second set of valves in sequence and in phase with thealternating current; and directing the direct current flow of ions intoa target tissue.
 13. The method of claim 12 wherein the first set ofvalves comprises a first and second pair of valves and the second set ofvalves comprises a third and fourth pair of valves.
 14. The method ofclaim 12 wherein the first and second set of valves are configured to beopened and closed and are further configured to switch in phase withalternating current applied to the electrodes.
 15. The method of claim12 further comprising using a conductor to direct the direct currentflow of ions into the target tissue.
 16. The method of claim 15 whereinthe conductor comprises a tube defining an elongate inner lumen.
 17. Themethod of claim 16 wherein the elongate inner lumen of the tube isfilled with a conductive material.
 18. The method of claim 17 whereinthe conductive material is an ionic solution or an ionic hydrogel. 19.The method of claim 13 further comprising closing the first set ofvalves when the third and fourth pair of valves are open.
 20. The methodof claim 13 further comprising closing the second set of valves when thefirst and second pairs of valves are open.